TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35505	106738;106739;106740	chr2:178529978;178529977;178529976	chr2:179394705;179394704;179394703
N2AB	33864	101815;101816;101817	chr2:178529978;178529977;178529976	chr2:179394705;179394704;179394703
N2A	32937	99034;99035;99036	chr2:178529978;178529977;178529976	chr2:179394705;179394704;179394703
N2B	26440	79543;79544;79545	chr2:178529978;178529977;178529976	chr2:179394705;179394704;179394703
Novex-1	26565	79918;79919;79920	chr2:178529978;178529977;178529976	chr2:179394705;179394704;179394703
Novex-2	26632	80119;80120;80121	chr2:178529978;178529977;178529976	chr2:179394705;179394704;179394703
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-166
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.0759
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
C/Y	rs2154132356	None	0.975	N	0.787	0.389	0.685049290349	gnomAD-4.0.0	1.63721E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.54388E-05	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
C/A	0.5827	likely_pathogenic	0.5479	ambiguous	-1.455	Destabilizing	0.177	N	0.432	neutral	None	None	None	None	N
C/D	0.9802	likely_pathogenic	0.9788	pathogenic	-0.114	Destabilizing	0.893	D	0.793	deleterious	None	None	None	None	N
C/E	0.9888	likely_pathogenic	0.9886	pathogenic	0.032	Stabilizing	0.893	D	0.799	deleterious	None	None	None	None	N
C/F	0.6453	likely_pathogenic	0.6529	pathogenic	-1.079	Destabilizing	0.928	D	0.796	deleterious	N	0.463831532	None	None	N
C/G	0.3103	likely_benign	0.2765	benign	-1.767	Destabilizing	0.474	N	0.739	prob.delet.	N	0.428508237	None	None	N
C/H	0.9481	likely_pathogenic	0.9435	pathogenic	-2.02	Highly Destabilizing	0.995	D	0.806	deleterious	None	None	None	None	N
C/I	0.8496	likely_pathogenic	0.859	pathogenic	-0.652	Destabilizing	0.944	D	0.771	deleterious	None	None	None	None	N
C/K	0.9874	likely_pathogenic	0.9865	pathogenic	-0.304	Destabilizing	0.893	D	0.795	deleterious	None	None	None	None	N
C/L	0.7956	likely_pathogenic	0.8054	pathogenic	-0.652	Destabilizing	0.705	D	0.679	prob.neutral	None	None	None	None	N
C/M	0.9104	likely_pathogenic	0.917	pathogenic	-0.154	Destabilizing	0.981	D	0.763	deleterious	None	None	None	None	N
C/N	0.9367	likely_pathogenic	0.9324	pathogenic	-0.512	Destabilizing	0.893	D	0.8	deleterious	None	None	None	None	N
C/P	0.9942	likely_pathogenic	0.9945	pathogenic	-0.894	Destabilizing	0.944	D	0.819	deleterious	None	None	None	None	N
C/Q	0.9615	likely_pathogenic	0.959	pathogenic	-0.298	Destabilizing	0.893	D	0.825	deleterious	None	None	None	None	N
C/R	0.9102	likely_pathogenic	0.9011	pathogenic	-0.583	Destabilizing	0.863	D	0.821	deleterious	N	0.481996253	None	None	N
C/S	0.5268	ambiguous	0.494	ambiguous	-0.987	Destabilizing	0.024	N	0.373	neutral	N	0.469565426	None	None	N
C/T	0.7739	likely_pathogenic	0.7732	pathogenic	-0.64	Destabilizing	0.544	D	0.679	prob.neutral	None	None	None	None	N
C/V	0.7453	likely_pathogenic	0.753	pathogenic	-0.894	Destabilizing	0.705	D	0.702	prob.neutral	None	None	None	None	N
C/W	0.9269	likely_pathogenic	0.928	pathogenic	-1.175	Destabilizing	0.993	D	0.767	deleterious	N	0.493606048	None	None	N
C/Y	0.8364	likely_pathogenic	0.8332	pathogenic	-1.018	Destabilizing	0.975	D	0.787	deleterious	N	0.462004735	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.